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Cytoreductive surgery and HITHOC, lung cancer

Intrathoracic Hyperthermic Chemotherapy (Hithoc) in advanced non-small lung cancer: the Nara Experience

As part of a continuing discussion of HITHOC (Hyperthermic IntraThoracic intraOperative Chemotherapy), today we are talking about the results of a small study conducted at the Nara Medical University, School of Medicine in Nara, Japan.

While the study is small (just 19 patients in three groups), it’s important because the patients involved all had advanced lung cancer, with malignant pleural effusions or disseminated disease discovered at the time of surgery. This is important, as readers know, because lung cancers are often diagnosed late, (after patients develop malignant effusions), and that the prognosis for patients with malignant effusions is grim.

Population: 19 patients.

Notably, the treatment group C consisting of seven patients (which received no intrathoracic thermic treatment) who were treated during an earlier period (2001 – 2003). Group C had an average age of 64. Essentially a control group.

The remaining patients were treated during 2006 – 2008 and are divided into two groups;

Group A which received hyperthermic (hot) saline infusion with a 30 minute dwell time – consisted of seven patients.  This group was also older (average age 72).

Group B, consisting of five patients who received hyperthermic chemotherapy (cisplatin) infusion into the chest cavity with a 30 minute dwell time.

Note: Infusion in this post refers to instillation of fluid into the chest cavity, not an intravenous treatment.    All patients received post-operative adjuvant chemotherapy.

The grouping of A and B serves to distinguish whether the mechanism of treatment is related to the application of heat alone, or the application of heated chemotherapeutic agents.  Current theories about the effectiveness of HITHOC suggest that the heat of the chemotherapy allows the drugs to penetrate more deeply into the tissues compared to application of chemotherapy alone, but requires studies such as this to support this theory.

Interestingly, the pre-operative staging of these patients differed significantly from intra-operative findings with 8 patients diagnosed with early disease (stage I), five patients with stage II and only six patients as stage IIIA pre-operatively.  (Presence of a pleural effusion denotes stage IV).  Malignant effusions were not seen during pre-operative workup. (It is not uncommon to find more advanced cancer at the time of surgery.)

Surgery: All of the patients underwent a VATS procedure (video-assisted thoracoscopy).  The majority of patients of patients (16) underwent surgery to remove the primary lesion (cytoreductive surgery) with ten patients undergoing lobectomy and six patients undergoing wedge resection.

Intra-operative findings:  16 patients found to have malignant effusions, 10 patients with disseminated disease.

Results: No intra-operative/ post-operative deaths.

Group A (hot saline group): no deaths during follow-up period, with a median follow-up period of almost 20 months.  No recurrence of pleural effusions.

Group B (heated chemotherapy group): 4 deaths in follow-up period; median survival time was 41 months, one patient with recurrent pleural effusion 26 months after treatment.

Group C: (VATs alone): 5 deaths (during follow-up period) median survival 25 months, 4 patients with recurrent pleural effusions (average time to recurrent effusion: 3 months).

While this study is too small (with only five patients receiving intrathoracic chemotherapy) to generalize the results – it should prompt researchers into conducting more studies and trials into the use of hyperthermic intrathoracic chemotherapy in patients with late stage lung cancers.

The decreased incidence of pleural effusion in the treatment groups (A and B) is important also for quality of life issues.  However, these findings are also limited by the small study size.

I have written to Dr. Naito (corresponding author on this article) for further comment and information.

Reference:

1. Kimura, M., Tojo, T., Naito, H., Nagata, Y., Kawai, N., & Taniquichi, S. (2010). Effects of a simple intraoperative intrathoracic hyperthermotherapy for lung cancer with malignant pleural effusion or dissemination. Interactive Cardiovascular & Thoracic Surgery 2010, April, 10 (4); 568 -71.  (linked to pdf).

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